This invention relates to new self-hardening synthetic material systems that harden under the influence of oxygen from the air which are used as surgical bonding or adhesive materials to bond hard body tissues and/or for the in situ formation of synthetic parts during surgical procedures in human and veterinary medicine. A particular property of the new synthetic materials which is obtained by this invention lies in its resorbability by metabolic actions of the body where, if desired, the time period of the resorption process can be controlled.
The rapid, durable joining of separated bones or the attachment of synthetic implants in either bones or dental materials is an old dream of surgeons. Until the present, mainly polymethacrylates, epoxide resins, and polyurethane systems have been investigated. In practice, only polymethacrylates have been used successfully. They are mainly used for the implantation of joint prostheses, the cementing together of metal and bone, fusion of vertebrae, the repairing of defects in the cranium, and the implantation of support materials in facial reconstructive surgery.
In addition to these applications, it is desirable to find additional areas of application for adhesives or cement for bones, such as in connection with anatomical repositioning, fixation, and retention of bone fragments for shattered fractures or joint breaks. It is desired to obtain a permanent joining of bone fragments and to obtain immediate use after hardening of the cement or adhesive material. It would be especially desirable to have the repositioning, fixing, and retention of bone fragments made reversible with the help of resorbable adhesive component systems. The adhesives or cement for the bones should be resorbed by the body as soon as the body has formed new bony material. In addition, it is important that the stabilizing of fractures by means of plates or splints be made reversible when they are attached by means of adhesives. The use of splints or plates made of metal or synthetic materials by the use of holes drilled in the bones and the application of screws would no longer be needed. When using resorbable supporting materials; for example, those made of polylactic acid or polyglycolic acid, the second operation could be omitted.
Adhesives or cements used for such purposes must, among others, meet the following requirements: chemical stability: maintenance of physical properties, even under the influence of body fluids within the required time range: biological compatibility: no carcinogenic properties: no allergenic properties or other sensitizing properties: complete mechanical use after hardening: in situ manufacture of the synthetic material parts in the desired shape: easily sterilizable: good curing time: and very little changes in volume or the development of heat during curing. Especially in the area of resorbable synthetic materials, there are present the additional requirements of resorbability within a given time frame by metabolic processes in the body, as well as freedom from damaging secondary reactions from by-products.
The methacrylate systems used up till now consist of the following components: one or more free radical polymerizable monomers, a free radical starter system to start the polymerization, polymers to improve cohesion and adjust the viscosity, and filler materials to improve the mechanical properties.
As polymerizable monomers, in addition to methylmethacrylate in combination with methacrylic acid, a number of other systems have become of practical importance--compare herewith J. M. Antonucci, Polymer Science and Technology, 14, 357 (1981). With respect to hardening systems for use at room temperature with polymerizable methacrylate systems, a broad pallet of accelerators is available today--compare, for example, G. M. Brauer, Org. Coat. Plast. Chem. 42, 321 (1980) as well as J. W. Prane, Org. Coat. Plast. Chem. 40, 338 (1979)--although improvements would be very desirable here.
It is also known that the adhesion of methacrylate adhesives on bony materials can be improved through boronalkyl hardeners. Boronalkyl compounds such as, for example, triethyl, tripropyl and tributyl borons are capable of initiating free radical polymerizations in the presence of oxygen from the air. They are therefore suitable as hardeners for two component methacrylate adhesives. See, in this connection, Japanese Patent Application Nos. 42 14 318 and 45 29 195 as well as German Patent Application No. 23 21 215. Japanese Application No. 42 14 318 suggests the use of trialkyl borons as hardeners for adhesives in dental medicine and as filler materials. When using trialkyl borons, there is obtained strengths which have not so far been obtainable with any other hardeners. The probable reason for this is that the trialkyl borons will initiate the graft polymerization of collagen--see Shikai-tenbo 32, 609 (1968). The adhesive or filler material will attach by means of a covalent chemical bond onto the tooth structure.
However, the use of trialkyl boron compounds, such as trimethyl, triethyl, tripropyl and/or tributyl boron presents unusual safety problems and technological difficulties. For example, triethyl boron has an ignition temperature of -20.degree. C. In order to alleviate such severe disadvantages, it has been suggested that the trialkyl boron compounds be reacted with amines or with controlled amounts of oxygen--see Japanese Application No. 45 29 195 and German Application No. 23 21 215. However, the spontaneous ignition of these systems is not thereby avoided. The ignition temperature is only shifted thereby into the temperature range of 0.degree. to 70.degree. C. Therefore, the manufacture of larger quantities of adhesives is impossible and their use limited accordingly.
In order to improve cohesion and to adjust to a viscosity which is preferred for application purposes, and to reduce the volume contraction during hardening, it is known to add polymers to the monomers, such as polymethyl methacrylate, polychloroprene, chlorosulfonated polyethylene, nitrile rubbers and/or polyurethanes--see e.g. U.S. Pat. Nos. 3,333,025; 3,725,504; 3,832,274; 3,890,407 and 3,994,764.
To improve hardness and shape stability, it was found advantageous to add filler material in finely divided form; crystalline systems due to their higher packing density than amorphous fillers are much superior--see, in this connection, A. K. Abell, et al, Pol. Sci. and Technology 14, 347 (1981).
The monomers used in adhesive systems, as well as the starter systems used therein, influence the stability of the adhesive. When bonding hard tissues in medicine, the resulting strength is dependent on the pretreatment of the bones and on the storage conditions of the fitted parts. For the use of adhesive systems in the animal body, bond strengths on degreased and dried bony tissues have little meaning. More relevant is the bonding of non-pretreated, damp and greasy bones and the strength measurements of the samples after storage in blood-Ringer solution. Under such simulated in vivo conditions, when using conventional methacrylate adhesives and bone cements on bone materials, there are obtained strengths of about 60 Ncm.sup.-2 (see, in this connection, G. Giebel et al, Biomed. Techn. 26, 170 (1981)). These strength values are too low for a number of areas of application, such as when joining bone fragments in order to obtain immediate usage thereof after hardening of the cement or adhesive. This results in a limitation in the application of these bone cements.
It is also known that certain synthetic materials will be decomposed by living organisms. Commercially available sutures based on polyglycolic acid or polylactic acid are resorbed by the organism. Use of these materials in dental medicine and orthopedic medicine are known. As far as the decomposition of these polymers are concerned, quantities of data are available--see, for example, R. A. Miller et al, J. Biomed. Mat. Res. 1977, 11, 711-719; D. C. Miln et al, Scot. Med. I, 17, 108 (1972) as well as A. M. Reed et al, Polymer 24, 499 (1981). By the co-condensation of glycolic acid and lactic acid, the rate of decomposition can be adjusted within a wide range--see, e.g., the above-mentioned literature citations.
Polyglycolic acid is usually obtained from glycolic acid through the intermediate step of glycolic anhydride with a suitable catalyst at a temperature in the range of 180.degree. to 200.degree. C. The direct polycondensation of glycolic acid at 118.degree. C. and 5 mbar will result in oligomeric products with low cohesion--see A. M. Reed et al, above.
Polyglycolic acid and/or polylactic acid have not been used in medicine as an adhesive or cement. Adhesives and cements should be applied in liquid form which, after application, will form a solid polymer. Based on their high required reaction temperature, the in situ manufacture of polyglycolic acid and polylactic acid is not possible for the bonding of substrates in the animal body.